Disease relevance of Tfrc

• On the contrary, increased transcription of the TfR gene in isolated nuclei was observed during reperfusion; during the ischemic phase this was preceded by enhanced binding of hypoxia inducible factor (HIF-1) to a DNA sequence derived from the TfR promoter [1].
• Tf-R immunoreactivity was detected in the ganglion cell layer, inner nuclear layer, outer plexiform layer, IS, RPE, and choroid [2].
• These findings suggest that 1) iron uptake by islet cells in vivo is regulated and mediated by TfR, 2) intracytoplasmic Ft transforms into stainable iron in iron-overloaded rats, and 3) predominance of TfR expression in B cells may result in selective deposition of iron and predispose B cells to damage and diabetes mellitus in iron-overloaded rats [3].
• Transferrin and transferrin receptor gene expression and iron uptake in hepatocellular carcinoma in the rat [4].
• Iron accumulation, iron-mediated toxicity and altered levels of ferritin and transferrin receptor in cultured astrocytes during incubation with ferric ammonium citrate [5].

Psychiatry related information on Tfrc

• Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease [6].
• The expression of many TH target genes is regulated by TH only for a limited critical period, although TH receptor (TR) expression is not greatly altered after such period [7].

High impact information on Tfrc

• Recently, the c-erb A proto-oncogene products have been shown to be nuclear thyroid hormone (T3) receptors (TR) by sequence similarity with other steroid receptors and by their ability to bind thyroid hormone [8].
• When conjugated to an antibody to the transferrin receptor, however, NGF crossed the blood-brain barrier after peripheral injection [9].
• Vesicles containing a dendritic protein, transferrin receptor (TfR), were preferentially transported into dendrites and excluded from axons [10].
• Since there are two major thyroid hormone receptor (TR) isoforms, TR alpha and TR beta, it is not known how the mutant receptor mediates a dominant negative effect [11].
• The synaptophysin-containing vesicles were labeled if a surface-labeled cell was warmed to 37 degrees C, comigrated with transferrin receptor-containing vesicles on velocity and density gradients, and could be completely immunoadsorbed by anti-LDL receptor tail antibodies [12].

Chemical compound and disease context of Tfrc

• The induction of transferrin receptor by ethanol might be one of the mechanisms of iron accumulation in the hepatocytes in alcoholic liver disease [13].
• Both desferrioxamine (DFO) and chloroquine can significantly reduce hepatic iron in experimental animals with iron overload by chelating iron from the low-molecular-weight pool or decreasing iron uptake by the transferrin-transferrin receptor cycle, respectively [14].
• To investigate this possibility, the effects of L-DOPA on the expression of iron influx proteins [transferrin receptor (TfR) and divalent metal transporter 1 (DMT1)], iron efflux protein (ferroportin 1), and iron uptake in C6 glioma cells were determined in this study using Northern blot and Western blot analysis and the calcein method [15].
• The disrupted protein-TfR mRNA interaction in the choroidal epithelial cells may explain the toxicity of manganese at the blood-CSF barrier [16].
• We have associated our study with the analysis of a transcriptional factor, the hypoxia inducible factor-1alpha (HIF-1alpha), known to control the expression of glucose transporter, and with a family of transcriptional factors, the thyroid hormone receptors (TR), regulating specific genes involved in brain development [17].

Biological context of Tfrc

• The molecular mechanisms controlling TfR gene expression in vivo during I/R of rat liver were investigated by molecular biology procedures [1].
• RNA bandshift analysis showed that iron regulatory protein (IRP) activity was decreased in the first hours of reperfusion, thus indicating that IRP-mediated mRNA stabilization was not involved in early TfR upregulation [1].
• In conclusion, HIF-1 mediated activation of TfR gene transcription and IRP-mediated increase of TfR mRNA stability ensure a steady induction of TfR, and hence higher iron uptake in reperfused rat liver [1].
• Transferrin receptor was found to be synthesized early in AEC cultures with the alveolar type II cell-like phenotype [18].
• These findings suggested that Tf-Fe transport across the membrane of astrocytes is mediated by Tf-TfR endocytosis [19].

Anatomical context of Tfrc

• TfR-mediated entry of the metal into liver cells may represent a source of catalytically active iron, which may play a role in reperfusion damage [1].
• In contrast, Tf, mainly synthesized by RPE cells and detected in OS and IS areas, probably helps to transport iron to photoreceptors through their Tf-R [2].
• Phenotype-dependent synthesis of transferrin receptor in rat alveolar epithelial cell monolayers [18].
• These data suggest that alveolar type II (but not type I) cells express functional transferrin receptor in adult rat alveolar epithelium [18].
• Inclusion of keratinocyte growth factor (KGF) in culture media (10 ng/ml) resulted in retention of transferrin receptor localized to the basolateral surface [18].

Associations of Tfrc with chemical compounds

• The level of transferrin receptor mRNA in cultured Sertoli cells was not influenced by hormones; however, chronic administration of testosterone or FSH to hypophysectomized rats resulted in increased transferrin receptor mRNA levels in the testis [20].
• Both up-regulation of ferritin content by iron application and up-regulation of TfR content by DFX were prevented by the protein synthesis inhibitor cycloheximide (CHX) [5].
• The distribution of transferrin, transferrin receptor, ferritin and ferric iron was studied in the developing rat brain [21].
• Hemin decreased surface TfR expression and counteracted the enhancing effects of desferrioxamine or succinylacetone on TfR expression [22].
• Comparison of iron-59, indium-111, and gallium-69 transferrin as a macromolecular tracer of vascular permeability and the transferrin receptor [23].

Physical interactions of Tfrc

• Antigenic material in rat plasma reacting with rat transferrin receptor antibodies was identified as an intact receptor molecule complexed with transferrin [24].

Enzymatic interactions of Tfrc

• In preliminary studies, monensin (10 microM) produced a 32%-50% shift of Tf-R from the surface to the inside, whereas short-term incubation with epidermal growth factor (0.17 mM) brought about no clear-cut Tf-R redistribution [25].

Co-localisations of Tfrc

• Rather, PS1 colocalized with transferrin receptor, a marker for early endosomes [26].

Regulatory relationships of Tfrc

• Such increases in tissue iron content may be attributed to the stabilisation of IRP-2 by aluminium thereby promoting transferrin receptor synthesis while blocking ferritin synthesis [27].

Other interactions of Tfrc

• Northern blot analysis of mRNAs from testes of rats synchronized at various stages of the cycle of the seminiferous epithelium showed that transferrin receptor mRNA was differentially regulated throughout the cycle [20].
• Manganese exposure altered the dynamics of IRP-1 binding and the intracellular abundance of IRP-2, and altered the cellular abundance of transferrin receptor, ferritin, and mitochondrial aconitase protein levels [28].
• Axons were enriched in synaptophysin immunoreactivity but did not contain detectable levels of transferrin receptor immunoreactivity [29].
• This decrease in proliferation was not associated with alterations in interleukin-2, interleukin-2 receptor, or transferrin receptor expression [30].
• Calmodulin dependence of transferrin receptor recycling in rat reticulocytes [31].

Analytical, diagnostic and therapeutic context of Tfrc

• Ferritin, Tf, and Tf-R proteins were localized by immunohistochemistry [2].
• HIF-1alpha, Tf, and TfR were measured by Western blot analysis and immunohistochemistry [32].
• Ferritin and Tf-R expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) and Tf expression by in situ hybridization (ISH) [33].
• Comparative study of Tf-R content was performed by slot-blot analysis and ferritin content was evaluated by enzyme-linked immunosorbent assay (ELISA) [33].
• The hepatocyte of the control group showed both cytoplasmic and membranous expression of TR [34].

References